The invention relates to liquid handling robots for well plates which are used in biochemistry and microbiology for processing large numbers of samples in parallel.
FIG. 1 is a perspective view of a liquid handling robot according to the prior art. The robot comprises a movable head 10 that is used for liquid handling and also has a mechanical manipulation capability. The head 10 is movable in three orthogonal axes, x, y and z, with respective motor positioners 12, 14 and 16. Head motion is controlled by a computer control system (not shown) via a control unit 15. The head 10 may also incorporates a camera (not shown) used to perform machine vision functions, such as bar code reading of well plates. The head 10 is movable over a main bed 18 of the apparatus on which well plates and other biological sample containers, such as Q-trays, petri dishes and omni-trays, can be arranged, usually within an experimental area 19. A waste chute 20 is incorporated in the main bed 18 and is flanked by stripping arm posts 21, the purpose of which is described below.
For mechanical manipulation, the head 10 is provided with pincers 25 which are used to grip pipette tip trays. Using the pincers 25 and the positioners 12, 14 and 16, the head 10 can be used to move pipette tip trays around the apparatus as required. The head 10 is also provided with jaws 26 arranged in the horizontal plane for gripping well plates or other sample plates such as omni-trays Q-trays or petri dishes.
FIG. 2 is a perspective view of a pipette tip tray 34 loaded with pipette tips 22. The pipette tips 22 are loaded into trays to allow robotic handling. Each tray is a flat piece of stiff material, such as metal or plastic, with an array of through holes in a grid conforming to the desired well plate standard grid, the through holes having a diameter equal to part of the tapered neck portion of the pipette tips 22, so that pipette tips 22 seat in the through holes.
For liquid handling, the head is provided with an array of pipette tip receiving cones 24 with the array being conformant to the well plate type being processed, for example a 12×8 array for 96-well well plates.
FIG. 3 shows a single pipette tip cone 24 together with an upper end of a pipette tip 22. Each cone 24 has a central capillary leading to a reservoir formed by a barrel and piston, in which the piston is slidable up and down in the barrel to provide a syringing action. The outer surfaces of the cones 24 are corrugated to assist pipette gripping. The cones are made of resilient material to aid formation of a liquid tight seal between themselves and the pipette tips 22 they are designed to receive.
Referring back to FIG. 1, arranged on the main bed 18 of the apparatus there can be seen a pipette tip tray anvil 32. The anvil 32 is a plate with an array of through holes in a grid conforming to one of the well plate standard grids, the through holes having a diameter slightly larger than the outer diameter of the widest part of the pipette tips 22.
A number of trays 34 loaded with unused pipette tips 22 are held in a shelved storage rack 36, sometimes referred to as a “hotel” in the art, with each tray arranged on one shelf and vertically adjacent shelves spaced far enough apart to avoid the pipette tips fouling each other when they are slid in and out of the shelves. In the schematic drawing, the hotel is illustrated as having three racks, each with three shelves. A greater number of shelves would usually be provided in practice.
The action of loading pipette tips 22 onto the liquid handling head 10 is now described. The head 10 is moved over to the pipette tip tray storage rack 36 and, using the pincers 25, one of the pipette tip trays 34 is taken out and placed on the anvil 32. The head 10 is then moved so that the array of cones 24 is aligned above the array of pipette tips 22. Using the lead screw motor drive of the z-positioner 16, the head 10 is then driven down so that the (male) cones 24 mate with the (female) upper apertures of the pipette tips 22, the anvil 32 acting as an abutment surface to allow the pipette tips 22 to be pushed onto the cones 24. The head 10 is then raised away from the anvil 32 using the z-positioner 16 with each of the cones 24 now loaded with a pipette tip 22 ready for liquid handling.
Once the desired pipetting action has been completed, the pipette tips, which are disposable items, can be removed from the head as now described. The head 10 includes a slotted plate (not shown), immediately above the cones 24 with the slots having a width greater than the maximum outer diameter of the cones and less than the maximum outer diameter of the pipette tips 22. The slotted plate is hinged to the main body of the liquid handling head 10. The hinging action allows ejection of pipette tips 22 from the cones 24 on which they are seated. The hinged slotted plate is actuated by a lever acting on the slotted plate being pushed onto the stripping posts 21 as the head 10 is driven down over the waste chute 20. The pipette tips are thus stripped off over the waste chute 20.
Some undesirable aspects of this design have been identified.
The anvil-based pipette tip loading process is not always reliable. The loaded pipette tips can on occasion fall off their cones, especially during syringing out of the liquid reservoir. If this happens, the resultant spillage can destroy the integrity of a whole well plate, which may contain valuable reagents and contain samples obtained from several processing steps already performed.
Manual loading of the pipette tip trays into the shelved storage rack is a fiddly, time consuming exercise, which needs to be performed with care in view of the fact that the pipette tips may be fragile and are held loose in their trays.
The liquid handling robot is not capable of performing other actions, such as gridding or picking, which necessitates transfer of the well plates to another machine if these actions need to be performed before or after the liquid handling actions. Each such transfer, carries a contamination risk, and is also inconvenient.